Abstract

Background

To identify the determinants of successful antiretroviral (ARV) therapy, researchers
study the virological responses to treatment-change episodes (TCEs) accompanied by
baseline plasma HIV-1 RNA levels, CD4+ T lymphocyte counts, and genotypic resistance
data. Such studies, however, often differ in their inclusion and virological response
criteria making direct comparisons of study results problematic. Moreover, the absence
of a standard method for representing the data comprising a TCE makes it difficult
to apply uniform criteria in the analysis of published studies of TCEs.

Results

To facilitate data sharing for TCE analyses, we developed an XML (Extensible Markup
Language) Schema that represents the temporal relationship between plasma HIV-1 RNA
levels, CD4 counts and genotypic drug resistance data surrounding an ARV treatment
change. To demonstrate the adaptability of the TCE XML Schema to different clinical
environments, we collaborate with four clinics to create a public repository of about
1,500 TCEs. Despite the nascent state of this TCE XML Repository, we were able to
perform an analysis that generated a novel hypothesis pertaining to the optimal use
of second-line therapies in resource-limited settings. We also developed an online
program (TCE Finder) for searching the TCE XML Repository and another program (TCE
Viewer) for generating a graphical depiction of a TCE from a TCE XML Schema document.

Conclusions

The TCE Suite of applications – the XML Schema, Viewer, Finder, and Repository – addresses
several major needs in the analysis of the predictors of virological response to ARV
therapy. The TCE XML Schema and Viewer facilitate sharing data comprising a TCE. The
TCE Repository, the only publicly available collection of TCEs, and the TCE Finder
can be used for testing the predictive value of genotypic resistance interpretation
systems and potentially for generating and testing novel hypotheses pertaining to
the optimal use of salvage ARV therapy.